Absent or reduced secretion of GH (isolated GH deficiency, IGHD) causes growth failure in children. The majority of IGHD cases is idiopathic, due to lack or deregulation of GHRH rather than to abnormalities in the somatotroph cells. Although most IGHD children grow in response to GHRH, due to GHRH short half-life they are commonly treated with daily injections of human recombinant GH (hGH). The same therapy increases final height in children with short stature who do not have biochemical evidence of GHD (idiopathic short stature, ISS). Based on this observation, hGH therapy has been recently approved by the FDA for children with severe ISS (stature < 1st percentile), increasing the number of American children that are candidates for hGH treatment to 410,000, with a yearly cost of $8 billion. Hence, the need for therapies that are less expensive than hGH, or can be administered less frequently or even orally. Such therapies should be aimed to directly increase the production of endogenous GH by the pituitary in the absence of GHRH. Potential therapeutic candidates are the Ghrelin analogues (GH secretagogues, GHS1), or long-acting GHRH analogues. Although several mouse models of GHD exist, none of them is suitable to test such therapies, as they cannot produce GH in response to exogenous stimuli. An ideal animal model would lack GHRH, and have normal development and function of the somatotroph cells. We have developed a mouse with generalized ablation (knock out, KO) of the GHRH gene (GHRHKO). GHRHKO mice have GHD but also severe somatotroph cells hypoplasia that limits their use to test potential IGHD therapies. Although hypoplasia can be reversed by GHRH treatment, such reversal is only partial. Therefore, we propose the creation of a mouse with temporal conditional ablation of the GHRH gene. We predict that this mouse will have normal somatotroph cell development, with IGHD acquired postnatally. This model will allow us to determine if GHS' have a significant direct effect on the somatotroph cells. In addition, it will mimic the clinical scenario that occurs in most children with IGHD, and it will be an important tool to study the effects of therapies aimed to increase the secretion of endogenous GH. [unreadable] [unreadable] [unreadable]